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Recent work has demonstrated an important link between intermediates of the citric acid cycle and the regulation of [[hypoxia inducible factors]] ([[HIF1A|HIF]]). HIF plays a role in the regulation of oxygen haemostasis, and is a transcription factor which targets angiogenesis, vascular remodelling, glucose ulitisation, iron transport and apoptosis. HIF is synthesized consititutively and hydroxylation of at least one of two critical proline residues mediates their interation with the von Hippel Lindau [[E3 ubiquitin ligase]] complex which targets them for rapid degradation. This reaction is calalysed by [[prolyl hydroxylase|prolyl 4-hydroxylase]]s. Fumarate and succinate have been identified as potent inhibitors of prolyl hydroxylases thus leading to the stabilisation of HIF.<ref>{{cite journal |author=Koivunen P, Hirsilä M, Remes AM, Hassinen IE, Kivirikko KI, Myllyharju J |title=Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF |journal=J. Biol. Chem. |volume=282 |issue=7 |pages=4524–32 |year=2007 |pmid=17182618 |url=http://www.jbc.org/cgi/content/full/282/7/4524}}</ref>

 

Most of the body's [[catabolic]] pathways converge on the TCA cycle, as the diagram shows. Reactions that form intermediates of the TCA cycle in order to replenish them (especially during the scarcity of the intermediates) are called [[anaplerotic reactions]].